Surg Today (2008) 38:1148–1151DOI 10.1007/s00595-008-3802-y

Reprint requests to: Y. EndoReceived: December 3, 2007 / Accepted: May 9, 2008

Splenectomy for Hypersplenism Caused by Adult T-Cell Leukemia: Report of a Case

YUICHI ENDO1, MASAYUKI OHTA

1, KOHEI SHIBATA1, SEIICHIRO KAI

1, KENTARO IWAKI1, HIROKI UCHIDA

1, MASAO OGATA

2, JUNJI IKEWAKI2, KENJI KASHIMA

3, and SEIGO KITANO1

1 Department of Surgery I, 2 Second Department of Internal Medicine, and 3 First Department of Pathology, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita 879-5593, Japan

AbstractA 45-year-old woman with previously diagnosed chronic type adult T-cell leukemia (ATL) presented with abdominal discomfort and red eruptions on her arms and legs. Anemia, thrombocytopenia, hypercalcemia, and splenomegaly indicated progression to acute-type ATL. Combined chemotherapy resulted in normaliza-tion of the serum calcium level and improvement in her symptoms. However, the severe anemia and thrombo-cytopenia persisted, necessitating transfusions of red blood cells (RBC) and platelets three times a week. We performed splenectomy in an attempt to reduce the total volume of malignant cells and improve the hyper-splenism. After the operation, the RBC and platelet counts increased gradually, and the transfusions were stopped on postoperative day (POD) 3. Splenectomy should be considered as an optional treatment for hypersplenism caused by ATL when hypersplenism cannot be controlled by chemotherapy in patients without a high surgical risk.

Key words Adult T-cell leukemia · Hypersplenism · Splenectomy

Introduction

Adult T-cell leukemia (ATL) is an aggressive malignant disease of the mature activated T cells, caused by human T-cell lymphotropic virus type 1.1–3 The prognosis asso-ciated with ATL is extremely poor, with median overall survival of less than 1 year. It has a geographic distribu-tion in southwestern Japan, the Caribbean, sub-Saharan Africa, Brazil, and northern Iran.4,5 Although many

cases of hypersplenism as a complication of ATL have been reported,6 there is no treatment strategy for the hypersplenism. We describe how splenectomy proved to be an effective treatment for hypersplenism caused by adult T-cell leukemia.

Case Report

A 45-year-old woman with chronic type ATL diagnosed 2 years earlier, based on high expression of serum human T-lymphotropic virus type 1 (HTLV-1) antibody and detection of HTLV-1 provirus in a blood examina-tion, presented with abdominal discomfort and red eruptions on the arms and legs. White blood cells (WBC) and ATL cells in the peripheral blood were elevated (WBC, 65.5 × 103/μl; abnormal lymphocytes, 83.0%). Anemia, thrombocytopenia, hypercalcemia, and splenomegaly were also recognized (red blood cells [RBC], 174 × 104/μl; hemoglobin, 6.4 g/dl; platelets, 24 × 103/μl; Ca, 10.7 mg/dl [8.2–10.2 mg/dl]; Table 1, Fig. 1). Progression to acute type ATL was diagnosed, and combined chemotherapy of THP-CEP (tetrahydropy-ranyl adriamycin 30 mg, etoposide 150 mg, cyclophos-phamide 500 mg, prednisolone 40 mg × 5 days) was initiated. About 1 month after she presented, the serum calcium increased further to 13.2 mg/dl, and she began to suffer symptoms such as high fever, nausea, drowsi-ness, and general fatigue. Thus, we changed the regimen of combined chemotherapy to CHOP (doxorubicin 30 mg, vincristine 3 mg, cyclophosphamide 500 mg, pred-nisolone 40 mg × 5 days). By 1 week later, the serum calcium level had normalized and her symptoms were improving, but the severe anemia and thrombocytope-nia persisted, necessitating blood transfusions of RBC and platelets three times a week (Fig. 2). As the spleen size was not decreasing, we decided to perform splenec-tomy to reduce the total volume of malignant cells and improve the hypersplenism.

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charged home on POD 24. About 1 month later, she received a pneumococcal vaccination (Pneumovax; Banyu Pharmaceutical, Tokyo, Japan) to prevent septic complications. In the 3 years since the splenectomy, the patient has been well without any signs of recurrence of acute type ATL.

Table 1. Laboratory fi ndings

WBC 65.5 × 103/μl TP 4.86 g/dl Stab 2.0% Alb 3.28 g/dl Seg 5.0% T-Bil 3.76 mg/dl Lymp 6.0% D-Bil 2.11 mg/dl Mono 4.0% AST 19.1 IU/l ABN-Ly 83.0% ALT 10.3 IU/lRBC 174 × 104/μl γ-GTP 56.2 IU/lHb 6.4 g/dl LDH 307 IU/lHct 20.8% Ca 10.7 mg/dlPlt 24 × 103/μl Fig. 1. Computed tomography scan before the operation

showed marked splenomegaly

Fig. 2. Clinical course and repeated blood transfusions. THP, tetrahydropyranyl adriamycin; VP-16, etoposide; CPA, cyclophos-phamide; PSL, prednisolone; DXR, doxorubicin; VDS, vincristine

Since the spleen was greatly enlarged, occupying the entire abdomen, laparoscopic splenectomy could not be performed, so the patient underwent conventional sple-nectomy with general anesthesia. The operation time was 130 min and the estimated blood loss was 400 ml. The resected spleen weighed 3500 g and measured 42 × 30 cm. Microscopically, there was diffuse infi ltration of ATL cells in the spleen (Fig. 3). Postoperatively, the RBC and platelet counts increased gradually, and blood transfusions were stopped on postoperative day (POD) 3 (Fig. 2). The patient had an uneventful postoperative course without evidence of portal vein thrombus. She received additional courses of CHOP and was dis-

1150 Y. Endo et al.: Splenectomy for Hypersplenism in ATL

Discussion

Adult T-cell leukemia is caused by an HTLV-1 infec-tion.1–3 Diagnosis is generally based on morphological analyses; namely, histological or cytological infi ltration by fl ower cells or malignant, activated lymphocytes with convoluted nuclei and basophilic cytoplasm, together with immunophenotype criteria. Adult T-cell leukemia is classifi ed into four subtypes according to the clinical course: acute type (incidence, 60%), lymphoma type (20%), chronic type (15%), and smoldering type (5%).7 A large study on ATL revealed that the median survival and 4-year survival rates were 6 months and 5.0% for the acute type, 10.2 months and 5.7% for the lympho-matous type, and 24.3 months and 26.9% for the chronic type, but over 13.3 months and 62.8% for the smolder-ing type, respectively.8

Most patients with moderate to massive splenomeg-aly complain of left upper quadrant pain and early satiety from the gastric compression. Hypersplenism, which is sometimes concomitant with malignant hema-tologic diseases such as leukemia, lymphoma, and myelofi brosis, may cause anemia and increased suscep-tibility to bleeding. Splenectomy is often performed for diagnostic or therapeutic reasons in patients with massive splenomegaly.9–11 To improve survival, splenec-tomy may be benefi cial for selected patients with marginal zone lymphoma (SMZL), characterized by low-grade lymphoma.12

To our knowledge, this is the fi rst report of hyper-splenism treated by splenectomy in a patient with ATL. In general, patients with malignant hematologic dis-eases have a high surgical risk, with morbidities after the splenectomy ranging from 3.5% to 61%.13–15 The most common and serious complications include disseminated intravascular coagulation, portal vein thrombosis, pulmonary embolism, atelectasis, pleural effusion, subphrenic abscess, and postoperative hemor-rhage.16–18 A splenic weight greater than 3000 g poses an especially high risk for portal vein thrombosis, with an incidence of 50%.18 Splenic size seems to be the most important preoperative predictor of postoperative complications.14

Our patient had massive splenomegaly and severe pancytopenia caused by hypersplenism. Chemotherapy proved ineffective in this regard and did not reduce the spleen size. Moreover, frequent transfusions of RBCs and platelets were required and pancytopenia was a major concern. Although a bone marrow biopsy was not done before splenectomy, we assumed that her severe pancytopenia was caused by hypersplenism for the fol-lowing reasons: the progression of pancytopenia was accompanied by spleen enlargement throughout the course, intensive chemotherapy associated with bone marrow failure was not given, and pancytopenia is rarely caused by the involvement of ATL cells in bone marrow. Therefore, although surgical intervention for such patients may still be on trial, we decided splenec-

Fig. 3. Microscopic examination of the spleen revealed diffuse infi ltration of lym-phoma cells. HE, hematoxylin–eosin; UCHL-1, ubiquitin carboxyl-terminal esterase L1

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tomy was justifi ed for this patient with ATL and uncon-trollable hypersplenism. Although we were concerned about the possible postoperative complications, sple-nectomy improved the patient’s general condition, including hematological data and symptoms. Her toler-ance for chemotherapy was also enhanced by the hema-tological improvement after splenectomy. Therefore, splenectomy may be appropriate for hypersplenism during chemotherapy.

In conclusion, we treated hypersplenism caused by ATL by performing splenectomy, with very favorable results. Thus, splenectomy should be considered as a choice of treatment for ATL when the hypersplenism is not controlled by chemotherapy in patients without a high surgical risk.

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